Scientific Inquiry

DR.S.SUNDARESAN
 AGENDA

1. RESEARCH QUESTION

2. SCIENTIFIC INQUIRY

3. BASIC SKILLS OF RESEARCHER

 Ordinary Versus Systematic

• Biased Question: A question that not leads

to a specific response or excludes a certain
group

– Nonscientific thinking leads to asking

questions that are slanted in a particular
direction
 Scientific Thinking
• It is common to think about in terms of
questions, observations, data, hypotheses,
testing, and theories. These are formal
parts of the scientific method.

• Most important parts of scientific thinking:

– using empirical evidence
– practicing logical reasoning
– possessing a skeptical attitude
 Research is ?
• Research is what we do when we have a question or
a problem we want to resolve
• We may already think we know the answer to our
question already
• We may think the answer is obvious, common sense
even
• But until we have subjected our problem to rigorous
scientific scrutiny, our 'knowledge' remains little
more than guesswork or at best, intuition.
• First priority is to formulate your question
• Then figure out how you are going to answer
it
– How have others answered it?
– How does your research fit in with what others
have done?
– How will you know when you have answered it?
 Hypothesis
• A hypothesis makes a prediction of the expected
outcome in a given situation
• Usually: how the manipulation of the independent
variable will influence the behaviour of a dependent
variable
• The hypothesis is tested in an experiment
• Statistical techniques try to help us show extent to
which our results really do support the hypothesis
 Experiment

• If the experiment works, the hypothesis is

shown to be probably correct
– Can’t prove 100% truth
• If it fails, it could be because
– The hypothesis is wrong
– The experimental design is faulty
• Where do we get our ideas from?
– Advisor/ Committee members/ colleagues
– Reading literature/publications
– Library/internet
– Conferences/seminars
– What is a great idea?
 Finding a topic
• Involves “informed” brainstorming
• It means researching and learning some things to help
narrow the focus.
• It means doing a “Literature search” to see what is
already known about the topic and to determine who
the experts are in the field

Operationalizing the research question

• Each component (variable) of the research question
needs to be defined in terms of the operations required
to measure them.
• These need to be specified in the Specific Aims section
of a study.
The FINER criteria for a good research question

• Feasible

• Adequate number of subjects

• Adequate technical expertise
• Affordable in time and money
• Manageable in scope
• Interesting

• Interesting to the investigator

Novel
• Confirms or refutes previous findings
• Extends previous findings
• Provides new findings

• Ethical

• Relevant

• To scientific knowledge
• To clinical and health policy
• To future research directions
THE 5 STEPS TOWARDS EVIDENCE BASED
PRACTICE
1. Ask the right clinical question:
Formulate a searchable question
2. Collect the most relevant publications:
Efficient Literature Searching
Select the appropriate & relevant studies
3. Critically appraise and synthesize the evidence.
4. Integrate best evidence with personal clinical expertise, patient preferences
and values:
Applying the result to your clinical practice and patient.
5. Evaluate the practice decision or change:
Evaluating the outcomes of the applied evidence in your practice or
patient.
THE QUESTION - WHY IS IT SO
IMPORTANT?

•A good answerable question will help us focus on

evidence that is relevant to a patient’s clinical needs, (or
your own knowledge needs).
•It can suggest high yield search strategies
•It can suggest the forms that useful answers might take
(i.e. what is best research design to answer our question)
 QUALITY OF A STUDY
The confidence that the study design, conduct and analysis has
minimized biases in addressing the research question
The better the quality, the higher is the likelihood that the results
produced in the study are credible
Validity
 The degree to which the results of an observation are correct
for the patients being studied.
Bias
 A process that tends to produce results that depart
systematically from the true values existing in the study
population.
Fletcher et al, 1988; Murphy, 1976
 SCIENTIFIC FOUNDATIONS OF RESEARCH

Several fundamental principles are used in scientific inquiry:

1. Order
The scientific method differs from ‘common sense’ in arriving at conclusions by employing an
organized observation of entities or events which are classified or ordered on the basis of
common properties and behaviours. It is this commonality of properties and behaviours that
allows predictions, which, carried to the ultimate, become laws.

Inference and chance

Reasoning, or inference is the force of advances in research. In terms of logic, it means that a
statement or conclusion ought to be accepted because one or more other statements or
premises (evidence) are true. Inferential suppositions, presumptions or theories may be so
developed, through careful construction, as to pose testable hypothesis. The testing of
hypothesis is the basic method of advancing knowledge in science.
Evaluation of probability
The critical requirement in the design of research, the one that ensures validity, is the evaluation
of probability from beginning to end. The most salient elements of design, which are meant to
ensure the integrity of probability and the prevention of bias, are: representative sampling,
randomization in the selection of study groups, maintenance of comparison groups as controls,
blinding of experiments and subjects, and the use of probability (statistical) methods in the
analysis and interpretation of outcome.

Hypothesis
Hypotheses are carefully constructed statements about a phenomenon in the population.
The hypotheses may have been generated by deductive reasoning, or based on inductive
reasoning from prior observations. One of the most useful tools of health research is the
generation of hypotheses which, when tested, will lead to the identification of the most
likely causes of disease or changes in the condition being observed. Although we cannot
draw definite conclusions, or claim proof using the inductive method, we can come ever
closer to the truth by knocking down existing hypotheses and replacing them with ones of
greater plausibility.
 Developing Your
Research Question

• I know what general area, but

• I’m not sure of my research question?
 From Interesting Topics to
Researchable Questions
An ‘angle’ for your research can come from
insights stemming from:

• personal experience
• theory
• observations
• contemporary issues
• engagement with the literature
 A Conventional View of Question
Formulation
• You must, first, pose a question that:
– Narrows down the ‘topic’ to a single problem
(and often to an hypothesis)
– Is not too big and not too small
– Builds on what is known
– Promises some new knowledge
– Will ‘last’ the duration of the research
 Narrowing and Clarifying

• Narrowing, clarifying, and even redefining

your questions is essential to the research
process.
• Forming the right ‘questions’ should be
seen as an iterative process that is informed
by reading and doing at all stages.
 Cycles of Research
Question Development
 STATEMENT OF PROBLEM

Three criteria of good Problem Statements.

1. A problem should be concerned with relation

between two or more variables.

2. It should be stated “clearly and unambiguously in

question form.”

3. It should be amenable to empirical testing

 CHARACTERISTICS OF A PROBLEM
A problem statement must have the following characteristics

1. It should ask about a relationship between two or more

variables.

2. It should be stated clearly and unambiguously, usually in

question form.

3. It should be possible to collect data or answer the questions

asked.

4. It should not represent a moral or ethical position.

DELIMITING A PROBLEM
Delimiting a problem is very important. A study should be
delimited by the following aspects:
1. A study should be delimited to certain variables that
should be mentioned clearly in the problem.

2. The study is delimited to the area or level as primary

level, secondary level, college or
university level.

4. Method of Research: A Problem or study may be

conducted by different methods but it is
not possible. Therefore, the best method should be used so
that the study should be delimited
to the method only.
5.Measuring Instrument: In behavioural science number of
instruments are available but all tools can not be used to
measure Thus the best available tool will be used for
measuring the variable.

6. Techniques of Research: A number of techniques can be

used for analysing data but most appropriate techniques
should be used.

7. The other limitation should vary from problem to problem

as every problem has its own delimitations.

8.Again study is delimited to size of sample. Considering the

time, energy and money, but it should be a representative.
EXERCISE
INTRODUCTORY CASE:
 A 45-year-old male with hypertension presents for follow up. At a prior
visit he was screened for diabetes.
 His hemoglobin A1C has been 7.0% on two occasions, which is a new diagnosis
of diabetes.
 His blood pressure is well controlled at 125/80.
 He has no evidence of microalbuminuria or kidney disease.

 You recall from College that ACEi are good for preventing diabetic
kidney disease, but you’re not sure if this fact applies to this patient.

 You want to find this answer.

 This module will walk you through the process of developing a clinical question!
BY THE END, YOU WILL BE ABLE TO:

 Explain the difference between

 Background and foreground questions

 Differentiate between
 Patient-oriented evidence and disease-oriented evidence

 Identify foreground questions and then apply the format to

create searchable clinical queries
 Population, Intervention/Comparison, Outcome
SO, HOW DO I DEVELOP A CLINICAL QUESTION?

 Two types of questions:

 1- Background Questions

 2- Foreground Questions Background

Questions
 Background questions ask “who, what,
where, when, why, or how” about a single
disease , drug, intervention, or concept.
EBM
Basic Clinical
 Think of these as basic questions you might Background
find from a textbook or a general EBM
resource
 Eg, prevalence, ddx, pathophys,
sensitivity/specificity of a test, med
dosing/adverse reactions
INTRO CASE:
BACKGROUND QUESTION BRAINSTORMING
 What are some background
questions that you can think Some possibilities/suggestions:
of related to our gentleman For diabetic kidney disease:
What is the mechanism?
with diabetes and HTN, What is the pathology?
related to the use of an ACE How does an ACEi work

inhibitor? to lower BP?

to reduce diabetic nephropathy?
 Who What dose of an ACEi do I prescribe?
Background What labs should I check for someone on an ACEi?
 What Questions
Potassium? Creatinine?
 Where How often?
What are the side effects of using an ACEi in patients with high
 When EBM blood pressure?
Basic Clinical
Background
 Why
 How
 SO, HOW DO I DEVELOP A CLINICAL
QUESTION?
 Two types of questions:
 1- Background Questions
 2- Foreground questions:
Foreground
Questions
 Foreground questions ask for specific knowledge
to inform a clinical issue on a specific patient,
intervention,or therapy.
General
 If based on expert opinion or best practices, they are Resources Research
guidelines. Studies
eg, Guidelines
 If based on EBM, they typically
compare two things (or against placebo) in a research
study:
 Diagnostic tests
 Drugs

 Treatments
THE QUESTION COMPONENTS
 Problem and Population
 What is the disease or condition?
P  What are the important characteristics of my patient?
 Intervention
 What is the intervention I am looking for?
 Is it realistic (availability, cost, convenience, etc)?
I C  Is this different from how I currently practice?
 Comparison
 What is the alternative to the intervention?
 Outcome
O  Is it something patients care about?
 Or is it something only physiologists/pharmacists
care about?
(Jackson, 2006; Flaherty, 2004)
SO, HOW DO I DEVELOP A CLINICAL
QUESTION? Focusing the question
 Population
 Starting with your patient, ask "How would I describe a
group of patients similar to mine?"
 Be precise but brief.
 Intervention/Comparison
 Ask “What is the main intervention I am considering?”
 and “What is the main comparison/control?”
 Be specific, but consider feasible alternatives.
 Outcomes
 Ask "What can I hope to accomplish?" or "What could this
exposure really affect?“
 Select patient-oriented outcomes instead of(University
“theofnumbers.”
Oxford EBM Tools, 2013)
INTRO CASE:
FOREGROUND QUESTION
BRAINSTORMING
 Problem/Population
 “In adult patients with diabetes mellitus II and
P hypertension”
 Intervention
 “Does an ACEi”
 Comparison
I C
 “Compared to placebo” or
“BB/CCB/diuretic/etc.”
 Outcome
 “Prevent development of microalbumuria?”
O
OR
 “Prevent worsening of eGFR?”
 THE PATIENT IS WHAT MATTERS

 Disease-Oriented Patient-Oriented Evidence That

Evidence (DOE) Matters (POEMs)

 Measures outcomes that  Measure outcomes that
are markers for disease our patients care about.
 “Silent  They have the potential
numbers” to change the way we
practice!

(Slawson , 1994)
CHARACTERISTICS OF DOES AND POEMS

 Disease-Oriented  Patient-Oriented Evidence That

Evidence (DOE) Matters (POEMs)
 Pathophysiology  Morbidity
 Lab values  Symptoms
 Biochemical markers  Daily function
 Pharmacology  Mortality
 Plaque size  Quality of Life
 Blood pressure  (as perceived by the
 Etiology patient)

(Slawson , 1994)
EXAMPLES OF DOES AND POEMS

 Disease-Oriented  Patient-Oriented Evidence That

Evidence (DOE) Matters (POEMs)
Intensive treatment can Intensive treatment in patients
lower blood glucose levels with type II diabetes does not
in patients with type II decrease mortality.
diabetes

Neither beta-carotene or
Beta-carotene and vitamin vitamin E prevent
E are good antioxidants cardiovascular disease or
cancer
(Tufts, 2013)
 DEVELOP A DOE AND A POEM FOR:
ACUTE OTITIS MEDIA
 Disease-Oriented
Evidence (DOE)
 Treating children with antibiotics can
sterilize the middle ear and treat
bacterial acute otitis media
 This pathological/pharmological
mechanism helps doctors determine
treatment
 But it does NOT focus on morbidity,
mortality, or quality of life
 In AOM, what do patients and parents
really care about?
 Patient-Oriented Evidence that
Matters (POEMs)
 Outcomes to focus on:
 Time course, pain, complications and side effects of
treatment
 Time course: Untreated AOM resolves by 1
week for 4 of 5 children
 Pain: Abx do not reduce pain at 1 day, but may
reduce it at 2 and 7 days follow up (quality of
life)
 Complications: Abx do NOT decrease incidence
of mastoiditis (morbidity)
 Side effects: Abx cause rash, diarrhea and
nausea with an equal likelihood as treatment
success (quality of life)
(Hoberman, 2011; Takata, 2001; Thompson, 2009)
INTRODUCTORY PICO QUESTION

 Patient
 “In adult patients with diabetes mellitus II and
P hypertension”
 Intervention
 “ACEi”
 Comparison
I C = DOE
 “Placebo”
 Outcome
 “Prevent worsening of eGFR?”

O Is eGFR an outcome
our patient cares about?
 POSSIBLE POEM ALTERNATIVES:

“In patients with diabetes, are ACEi associated with lower

mortality rates?”

Or
“In patients with diabetes, do ACEi delay progression
toward end-stage kidney disease requiring dialysis?”

Or
“In patients with diabetes, do ACEi delay progression
toward end-stage kidney disease requiring a kidney
transplant?” (Cochrane, Lv 2012)
 ALTERNATE CLINICAL QUERIES

 After developing a “best” case-based question, the next step is

exploring other searchable clinical queries.
 These are a list of flexible alternative questions since the answer to
your precise question may not match the current scientific
literature.
P  Typically the alternatives involve reasonable variations of your
interventions/comparison or alternative outcomes.
I C

(Cochrane, Lv 2012)
 CASE 1:

 A 35-year-old migrant farm worker presents to your clinic for

follow-up visit.
 A few weeks ago at a health fair, his blood pressure was 170/98.
 Today on follow up, his vitals are
 T 98, P 88, R 16, BP 166/100, O2 99%
 You diagnose him with hypertension and to guide medical
treatment.
 He asks you: “Do I need medication, doctor?”

(JAMA; James, 2014)

 SO, HOW DO I DEVELOP A CLINICAL
QUESTION?
 List
the questions you had and still have.
 Focus on a foreground question.
 Rephrase it into a PICO format.
 P: Be precise but brief
 I/C: Be specific, but consider feasible alternatives
 O: Select patient-oriented outcomes instead of “the numbers.”
QUESTION—CASE

P  P- population
 I- intervention
 C- comparison group
I C  O- outcome (make it patient oriented)

O
Answer?
 FOREGROUND QUESTION SEARCHES

 “Developing Clinical Questions” is just the beginning of

information mastery on how to answer clinical questions.
 “Finding Answers to Clinical Questions”
 To minimize your work in selecting sources
 To locate valid and relevant information
 To maximize your learning in navigating information mastery
search engines and resources
 To help you answer the questions you’ve developed today!
Basic skills for a laboratory researcher

• Productivity
– Ability to carry out a project to completion and
fruition
– Ability to prioritize and focus on high priority
items
– Ability to carry out more than one project
simultaneously and efficiently through detailed
planning
• Scientific attitude: Desire to get the bottom of things
Resistant the idea of coming to the premature
conclusion that things cannot be better understood or
improved
– Willingness to “bite the bullet” to spend some time
and effort to make things better and/or more
efficient
– Not afraid to learn new things
– Wanting to fully understand everything including
the instruments in the experiment
– Not willing to leave any “mysteries” or poorly
understood phenomenon behind
– Low tolerance for “black box”
• Good citizenship in a laboratory
– Willingness to help and collaborate with
colleagues
– Being a considerate colleague
• Take assigned lab responsibilities seriously
• Ordering lab stocks and common supplies in
time
• Never leave a mess in public areas
• Keep a clean and neat bench instead of a eye
sore
• Clean up your bench and shelves at the end of
the day
• Help maintain and fix instruments
• Paper reading (will be introduced in another text)
– Critically and actively
– Ability to recognize problems in the experimental
design
– Ability to recognize key sentences
• Understanding and use of the literature
– Ability to evaluate a paper critically and accurately
– Familiarity to a broad-based, relevant and current
literature
– Ability to generate useful notes while reading the
literature
– Ability to generate interesting and important questions
– Ability to generate original ideas on the literature
• Experimental design
– Ability to get techniques to work predictably and
reproducibly
– Ability to generate high quality data with both positive and
negative controls that can give clear cut answer to a
question
– Ability to find the best available information from the best
sources
– Ability to interpret fully your data, generate next question
or hypothesis and design the next experiment
– Ability to troubleshoot and solve a technical problem
– Resistance to doing an incomplete experiment using
whatever reagents or cells that happen to be available ”to
see what happens”
• Paper writing
– Ability to group data in a logical fashion into good
figures
– Ability to make a good-looking figure
– Ability to interpret data in relation to existing
literature and come up with new ideas
– Ability to write a good and useful first draft
– Ability to use key sentence